This program, thus far, has stimulated the development of highly specific, surgically non-invasive, time-varying, electromagnetic fields (EMF's) which increase bone formation in animals and humans with fractures, pseudarthroses, and osteoporosis. Far more is known, however, in the neo-natal period of this new electrotherapeutic modality, about the technical aspects of achieving a therapeutic result than is known about the mechanisms by which the result is achieved. The proposed research for the next three years, therefore, will focus on the interaction between pulsing electromagnetic fields and cellular responses, particularly, as they relate to growth, cell differentiation and/or specialization, synthesis of macromolecules, and transfer of ions across the plasma membrane. Tissue culture, experimental surgical, histochemical, biochemical ultrastructural and analyses will be employed in a coordinated, multidisciplinary approach to data gathering and analysis. Results will have, not only scientific importance in defining the physiologic selectivity of EMF's with specific pulse characteristics, but will aid in increasing their therapeutic effectiveness in diseases and disorders of the musculoskeletal system.